Despite advances in care, asthma world-wide continues to increase and to produce significant morbidity and possibly increasing mortality. Various pharmacologic strategies have had a significant impact, but it is hoped that insights into the pathophysiology of asthma may suggest new approaches to therapy. Recent studies have focused on the importance of inflammatory and immune mechanisms. This proposal examines the mechanisms and consequences of leukocyte adhesion in asthma, focusing on adhesion blockade of leukocytes residing within the lung rather on circulating leukocytes migrating into the lung. These studies utilize a mouse model of asthma that replaces the cardinal features of the human disease. The Specific Aims of the proposal are: 1) To characterize the role of intrapulmonary CD49d (alpha4-integrin) in allergen-induced lung inflammation and airway hyperreactivity (AHR); 2) To define the mechanisms by which CD49d blockade inhibits allergen-induced lung inflammation and AHR; 3) To determine the contribution of intrapulmonary CD49a (alpha1- integrin) and other leukocyte integrin matrix receptors to allergen- induced lung inflammation and AHR; 4) To determine the effect of an intrapulmonary isoprenoid synthesis inhibitor on allergen-induced lung inflammation and AHR; 5) To determine the role of dendritic cell migration in allergen-induced lung inflammation and AHR. These studies address previously unexplored areas of integrin biology and pulmonary immune responses and have the potential to suggest new approaches to therapy in asthma.